The pacific islands of Micronesia have experienced several outbreaks of mosquito-borne diseases over the past decade. In outbreaks on small islands, the susceptible population is usually well defined, and there is no co-circulation of pathogens. Because of this, analysing such outbreaks can be useful for understanding the transmission dynamics of the pathogens involved, and particularly so for yet understudied pathogens such as Zika virus. Here, we compared three outbreaks of dengue and Zika virus in two different island settings in Micronesia, the Yap Main Islands and Fais, using a mathematical model of transmission dynamics and making full use of commonalities in disease and setting between the outbreaks...

In the past, divergent results have been reported based on different methods and conditions used for enzymatic activity measurements of cytochrome c oxidase (CytOx). Here, we analyze in detail and show comparable and reproducible polarographic activity measurements of ATP- dependent inhibition of CytOx kinetics in intact and non-intact rat heart mitochondria and mitoplasts. We found that this mechanism is always present in isolated rat heart mitochondria and mitoplasts; however, it is measurable only at high ATP/ADP ratios using optimal protein concentrations...

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening inflammatory syndrome characterized by hyperactivation of lymphocytes and histiocytes. T cells play a key role in HLH pathogenesis, but their differentiation pattern is not well characterized in patients with active HLH. We compared T-cell activation patterns between patients with familial HLH (1°HLH), 2°HLH without apparent infectious trigger (2°HLH) and 2°HLH induced by a viral infection (2°V-HLH). Polyclonal CD8(+) T cells are highly activated in 1°HLH and 2°V-HLH, but less in 2°HLH as assessed by HLA-DR expression and marker combination with CD45RA, CCR7, CD127, PD-1 and CD57...

The excessive CO2 emissions in the atmosphere from anthropogenic activity can be divided into point sources and diffuse sources. The capture of CO2 from flue gases of large industrial installations and its conversion to fuels and chemicals with fast catalytic processes seems technically possible. Some emerging technologies are already being demonstrated on an industrial scale. Others are still being tested on a laboratory or pilot scale. These emerging technologies can be implemented in a time-window ranging from 5 to 20 years...

In cancer cells, the reversible nature of the stemness status in terms of chemoresistance has been poorly characterized. In this study, we have simulated on cycle of environmental conditions to study such reversibility by first generating floating tumorspheres (FTs) from lung and breast cancer cells by culturing them in serum-free media without the addition of any external mitogenic stimulation, and subsequently (after two weeks) re-incubating them back in serum-containing media to simulate routine culture conditions (RCCs)...

There has recently been significant interest within the vibrational spectroscopy community to apply quantitative spectroscopic imaging techniques to histology and clinical diagnosis. However, many of the proposed methods require collecting spectroscopic images that have a similar region size and resolution to the corresponding histological images. Since spectroscopic images contain significantly more spectral samples than traditional histology, the resulting data sets can approach hundreds of gigabytes to terabytes in size...

A reliable protocol has been established for in vitro propagation of Artemisia nilagirica var. nilagirica (Indian wormwood), a valuable medicinal plant from India. A highly proliferating organogenic callus was obtained on Murashige and Skoog (MS) medium supplemented with 2.5 µM IAA when nodal explants were cultured on MS medium supplemented with various growth regulators. Further, highest regeneration frequency (83.3 %) of adventitious shoots was observed, when the callus was sub-cultured on MS medium supplemented with 6-benzylaminopurine (BAP; 2...

BACKGROUND AND PURPOSE: Detailed data on the occurrence of swallowing dysfunction in patients with recent small subcortical infarcts (RSSI) in the context of cerebral small vessel disease are lacking. This prompted us to assess the frequency of and risk factors for dysphagia in RSSI patients. METHODS: We identified all inpatients with magnetic resonance imaging-confirmed RSSI between January 2008 and February 2013. Demographic and clinical data were extracted from our stroke database, and magnetic resonance imaging scans were reviewed for morphological changes...

OBJECTIVE: The objective for this study was to investigate the effects of prior familiarization with takeover requests (TORs) during conditional automated driving on drivers' initial takeover performance and automation trust. BACKGROUND: System-initiated TORs are one of the biggest concerns for conditional automated driving and have been studied extensively in the past. Most, but not all, of these studies have included training sessions to familiarize participants with TORs...

Brown adipose tissue (BAT) is key to energy homeostasis. By virtue of its thermogenic potential it may dissipate excessive energy, regulate body weight, and increase insulin sensitivity. Catecholamines are critically involved in the regulation of BAT-thermogenesis, yet research has focussed on the effects of noradrenaline and adrenaline. Some evidence suggests a role of dopamine (DA) in BAT-thermogenesis but the cellular mechanisms involved have not been addressed. We employed our extensively characterised murine brown adipocyte cells...

A unique resource for systems pharmacology and genomic studies is the NCI-60 cancer cell line panel, which provides data for the largest publicly available library of compounds with cytotoxic activity (~21,000 compounds), including 108 FDA-approved and 70 clinical trial drugs as well as genomic data, including whole-exome sequencing, gene and microRNA transcripts, DNA copy number, and protein levels. Here we provide the first readily usable genome-wide DNA methylation database for the NCI-60, including 485,577 probes from the Infinium HumanMethylation450k BeadChip array, which yielded DNA methylation signatures for 17,559 genes integrated into our open access CellMiner version 2...

EZH2 (enhancer of zeste homologue 2) is the catalytic subunit of the polycomb repressive complex 2 (PRC2) that catalyzes the methylation of lysine 27 of histone H3 (H3K27). Dysregulation of EZH2 activity is associated with several human cancers and therefore EZH2 inhibition has emerged as a promising therapeutic target. Several small molecule EZH2 inhibitors with different chemotypes have been reported in the literature, many of which use a bicyclic heteroaryl core. Herein, we report the design and synthesis of EZH2 inhibitors containing an indoline core...

Chronical alcohol abuse causes more than 200 diseases and/or symptoms and among these alcoholic liver disease (ALD) is of special importance since it occurs frequently and may be life-threatening. In Europe alcohol consumption as well as ALD increased as compared to the rest of the world. It has been estimated that in Europe approximately 500 000 people die every year due to ALD. ALD consists of alcoholic fatty liver, alcoholic steatohepatitis (ASH), alcoholic cirrhosis and hepatocellar cancer (HCC ). Alcohol hepatitis (AH) is a clinical feature with jaundice and liver failure and a high mortality...

Pain is necessary to alert us to actual or potential tissue damage. Specialized nerve cells in the body periphery, so called nociceptors, are fundamental to mediate pain perception and humans without pain perception are at permanent risk for injuries, burns and mutilations. Pain insensitivity can be caused by sensory neurodegeneration which is a hallmark of hereditary sensory and autonomic neuropathies (HSANs). Although mutations in several genes were previously associated with sensory neurodegeneration, the etiology of many cases remains unknown...

OBJECTIVE: To evaluate the safety and efficacy of TX-004HR vaginal estradiol soft-gel capsules for moderate-to-severe dyspareunia associated with postmenopausal vulvar and vaginal atrophy. METHODS: In this randomized, double-blind, placebo-controlled, phase 3 study, postmenopausal women with a self-identified most bothersome symptom of dyspareunia received 4, 10, or 25 μg TX-004HR or placebo for 12 weeks. Four co-primary efficacy endpoints were change from baseline to week 12 in percentages of superficial and parabasal cells, vaginal pH, and severity of dyspareunia...

Slope failure like in the Hinlopen/Yermak Megaslide is one of the major geohazards in a changing Arctic environment. We analysed hydroacoustic and 2D high-resolution seismic data from the apparently intact continental slope immediately north of the Hinlopen/Yermak Megaslide for signs of past and future instabilities. Our new bathymetry and seismic data show clear evidence for incipient slope instability. Minor slide deposits and an internally-deformed sedimentary layer near the base of the gas hydrate stability zone imply an incomplete failure event, most probably about 30000 years ago, contemporaneous to or shortly after the Hinlopen/Yermak Megaslide...

Lung cancer is the leading cause of cancer deaths, and effective treatments are urgently needed. Loss-of-function mutations in the DNA damage response kinase ATM are common in lung adenocarcinoma but directly targeting these with drugs remains challenging. Here we report that ATM loss-of-function is synthetic lethal with drugs inhibiting the central growth factor kinases MEK1/2, including the FDA-approved drug trametinib. Lung cancer cells resistant to MEK inhibition become highly sensitive upon loss of ATM both in vitro and in vivo...

A series of thermoresponsive glycomicrogels with trehalose in the cross-links or with trehalose in the cross-links and as pending moieties was synthesized. These materials were obtained by surfactant-free precipitation copolymerization of N-isopropylacrylamide and various amounts of trehalose monomers. The resultant particles showed a spherical shape and a submicrometer hydrodynamic size with a narrow size distribution. At 25 °C, glycomicrogels in solutions with physiological ionic strength formed stable colloids, which further gelled upon heating to physiological temperature forming a macroscopic hydrogel with an interconnected porous structure...